# Targeting Cancer Stem Cells

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2020 · $228,058

## Abstract

Project 1
Project Summary
Therapeutic advances over the past 3 decades now allow most hematologic malignancy patients to achieve
major clinical responses. Although the responses can clearly decrease side effects and improve quality of life,
most patients still eventually relapse and die of their disease. Our work suggest that the cancer stem cell (CSC)
concept may explain why dramatic responses often fail to translate into cures. We found that relapse in many
cancers appears to result from rare cells with stem cell characteristics; these so-called CSCs are often
biologically distinct from their progeny that form the bulk of the tumor, notably exhibiting substantially different
sensitivity to drugs. The rapid responses induced by chemotherapies in most hematologic malignancies are likely
a consequence of their impressive activity toward the bulk of the tumor, against which the treatments were
developed. The limited durability of many of these responses is consistent with our data showing that the CSCs
are often relatively resistant to such therapies. Unfortunately, despite the explosion of work in the area of CSCs,
there continues to be few clinical trials studying the therapeutic targeting of these cells and even fewer clinical
trials offering "proof" of the CSC concept that targeting these cells will actually improve outcomes. Our studies
have also shown that mismatched allogeneic blood or marrow transplantation (BMT) employing post-
transplantation cyclophosphamide (PTCy) is now safe and effective, allowing nearly all patients in need of BMT
to undergo this procedure. With issues of donor availability, GVHD, and non-relapse mortality (NRM) now taking
on lesser importance in alloBMT, relapse has become by far the major concern. Emerging data suggest that a
new, non-tolerant, and non-exhausted transplanted immune system has the ability to augment the activity of
many anticancer agents, small molecule as well as immunologic. The MRD state post-alloBMT provides
additional advantages for antitumor approaches, in that they will be utilized at lowest tumor burden as well as
least tumor heterogeneity including being enriched for CSCs. Accordingly, the overall hypothesis of this Project
is that targeting MRD in patients at high-risk for relapse after BMT with CSC-directed therapy, will improve
disease control. The overall objective is to explore approaches that target leukemia and multiple myeloma (MM)
CSCs and translate promising treatments into clinic in the setting of MRD after alloBMT. Since targets being
studied are expressed primarily by AML (CD123) and myeloma (CD19) CSCs rather than the respective bulk
tumor, if successful, these data should also provide strong evidence in support of the CSC concept.

## Key facts

- **NIH application ID:** 9932943
- **Project number:** 5P01CA225618-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RICHARD J JONES
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,058
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932943

## Citation

> US National Institutes of Health, RePORTER application 9932943, Targeting Cancer Stem Cells (5P01CA225618-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932943. Licensed CC0.

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